tbuckley/cabot-search huggingface dataset:
Juvenile myelomonocytic leukemia: A national analysis of demographic features.
Authors: Maximillian Whooley, Beau Hsia, Darby Keirns, Andrew Luker, Peter T. Silberstein, Xinxin Wu
Journal: Journal of Clinical Oncology (2023)

e19086 Background: Juvenile Myelomonocytic Leukemia (JMML) is a rare hematological cancer originating in the bone marrow. It is a type of myelodysplastic syndrome (MDS) characterized by abnormal production of myeloid progenitor cells and monocytes. This malignancy is predominant in males, has a median age of diagnosis of 2 years, and carries a poor prognosis. It only accounts for 1% of all pediatric leukemias but constitutes 20-40% of pediatric MDS cases, making it the most common MDS subtype in children. Hematopoietic stem cell transplant (HSCT) is the only known cure for JMML, but its efficacy is just 50%. Without treatment, patients survive for a median of 10-12 months. Given the rarity of JMML, an analysis of demographic trends could offer valuable epidemiological insight. The National Cancer Database (NCDB) database was used to examine major demographic features of JMML. Methods: A retrospective analysis of all patients diagnosed with JMML between 2004 – 2020 in the NCDB (N = 242) was performed. Demographic factors including sex, race, Hispanic ethnicity, household income status, insurance status, urban/rural status, and Charlson-Deyo score were examined by descriptive statistics. Treatment statistics were also analyzed. Linear regression was used to determine incidence trends. Results: A total of 242 patients were identified with a histologically-confirmed diagnosis of JMML. Most patients were male (67.4%). The average age of diagnosis was 2 years (SD = 3.69, range = 0-33). The average incidence was 14.2 patients diagnosed per year (SD = 3.7, range = 9 – 21, R2 = 0.131). 93.8% had a Charlson-Deyo comorbidity score of 0. The majority of patients were White (74.4%), followed by Black (11.6%). 16.1% of patients were of Hispanic ethnicity. The distribution of median household income was 27.4% in the top quartile, 26.9% in the second, 26.9% in the third, and 18.7% in the fourth. Most patients were either privately insured (49.6%) or insured by Medicaid (42.6%). 75.5% of patients lived in a county with 250,000 people or more. Most patients received treatment (84.6%), while some only received active surveillance (8.7%) or no treatment (6.7%). Conclusions: This is the first NCDB analysis describing the demographic trends of JMML. Patients were twice as likely to be male than female. They were most likely to be White, with an average age of 2 years. This data reflects the expected age group and sex/race predominance described in the literature. The proportion of Hispanic JMML patients was comparable to Hispanics in the general US population. JMML appeared to be nearly evenly distributed among the top three household income quartiles. The lowest income quartile and rural inhabitants were least affected by this disease, which may indicate underdiagnosis in these populations. Further studies are needed to better define the relevance of these individual factors in the diagnosis, treatment, and survival of patients with JMML.
Outcomes of patients with small cell lung cancer admitted to the intensive care unit.
Authors: Joy Huang, Daniel H Kwon, Sam Brondfield
Journal: Journal of Clinical Oncology (2023)

e20620 Background: Small cell lung cancer (SCLC) is aggressive and carries a poor prognosis. National Comprehensive Cancer Network guidelines recommend considering systemic therapy even for patients with poor performance status, if cancer-related. However, little is known about the prognosis and effectiveness of treatment for patients with SCLC in the intensive care unit (ICU), and thus clinicians lack guidance in this scenario. Therefore, we characterized outcomes and predictors of overall survival (OS) for patients with SCLC in the ICU for cancer-related complications, with or without chemotherapy. Methods: This is a single-institution retrospective study in which we used diagnosis codes to identify all patients with SCLC who were admitted to the ICU from 2012 to 2022. We then manually selected patients admitted to the ICU for cancer-related complications and excluded those admitted for chemotherapy complications, post-operative observation, or other reasons not directly related to SCLC. Demographic and clinical data were collected via manual chart review. OS from ICU admission date was evaluated using the Kaplan-Meier method and compared between those who received chemotherapy and those who did not using the log-rank test. Multivariate analysis was performed using Cox proportional hazards regression analysis to identify predictors of OS. Sensitivity analysis was performed by excluding patients with limited stage (LS) disease. Results: Twenty-three patients met inclusion criteria, of whom 20 had extensive-stage (ES) and three had LS disease. Six patients received chemotherapy in the ICU (five with ES, one with LS) and 17 did not. Of those who received chemotherapy, two died during their stay, and four had partial responses. Median OS from ICU admission for all patients was 2.4 weeks. Median OS from ICU admission did not differ significantly between those who received chemotherapy and those who did not (21.0 vs 1.6 weeks, p = 0.12). A three-variable model significantly predicted OS: pulmonary vs non-pulmonary reason for ICU admission (HR for death = 6.18 [95% CI 2.01-19.00], p &lt; 0.01), TNM stage IVB vs IVA or III (HR = 5.34 [1.58-18.00], p = 0.01), and Charlson Comorbidity Index (HR = 0.76 [0.56-1.04], p = 0.09). Results were similar when patients with LS disease were excluded. Conclusions: In this single-institution study of patients with SCLC admitted to the ICU for cancer-related complications, OS was short. Chemotherapy given in the ICU was not associated with longer OS. Potential clinical predictors of OS at the time of ICU admission were identified: pulmonary reason for ICU admission and TNM stage IVB were both associated with shorter OS. The trend toward improved OS associated with higher Charlson comorbidity index may reflect reversible non-malignant contributors to ICU-level illness. Conclusions apply primarily to patients with ES disease. These findings require validation in larger, multicenter studies.
Efficacy and safety of nivolumab and trabectedin in pretreated patients with advanced soft tissue sarcomas (STS): Results of a phase II trial of the German Interdisciplinary Sarcoma Group (GISG-15, NitraSarc).
Authors: Peter Reichardt, Dimosthenis Andreou, Anne Flörcken, Thorben Groß, Stephan Richter, Torsten Kessler, Martin Kortüm, Christian Andreas Schmidt, Bernd Kasper, Eva Wardelmann, Atzler Benedict, Disorn Sookthai, Daniel Wilhelm Mueller, Daniel Pink
Journal: Journal of Clinical Oncology (2023)

11500 Background: Programmed death-1 (PD-1) inhibitors alone have modest activity in the treatment of most STS. A possible synergistic effect of combined trabectedin with PD-1 inhibitor nivolumab has been previously reported. Herein we evaluated the efficacy and safety of trabectedin plus nivolumab as a second-line treatment of patients with anthracycline-pretreated metastatic or inoperable STS. Methods: The prospective, explorative, two-group, non-randomized phase II NiTraSarc trial enrolled patients with advanced lipo- or leiomyosarcomas (Group A; GA) or with non-L-sarcomas (Group B; GB). Patients were initially treated with 3 cycles of trabectedin 1.5 mg/m 2 , followed by the combination of trabectedin 1.5 mg/m 2 plus nivolumab 240 mg in a so-called “late combination cohort” (LCC) for up to 16 cycles. After positive results of a preplanned interim analysis, patients received the combination therapy already starting from Cycle 2 in an “early combination cohort” (ECC). Primary efficacy endpoint was progression-free survival rate after 6 months (PFSR6) according to RECIST v.1.1. A central pathological assessment (CPA) was done from tumor specimen from all patients. Updated results according to cpa are presented. Results: A total of 92 patients were recruited in the trial: 43 patients in GA and 49 in GB. In GA, 28 patients (63%) had leiomyosarcoma and 15 (37%) had liposarcoma. Most common sarcoma types in GB were pleomorphic (n = 12), spindle cell (n = 11), fibromyxoid (n = 6), synovial (n = 5) and epithelial (n = 4) sarcoma. After median follow up of 16.6 months, overall PFSR6 as per CPA in GA was 47.6% (60% in LCC vs 36.4% in ECC) and 14.6% in GB. Median PFS was numerically higher in GA compared to GB (5.5 vs 2.3 months) and even longer in LCC vs ECC (9.8 vs 4.4 months). Median overall survival was more than three times longer in GA vs GB (18.7 vs 5.6 months) and, again, longer in LCC vs ECC (24.6 vs 13.9 months). Safety trabectedin and nivolumab was consistent with the safety profiles of each drug alone with no relevant new findings for the combination or between LCC and ECC. Conclusions: Our study confirms the activity of trabectedin plus nivolumab, particularly in patients with lipo- or leiomyosarcomas. There is a significant difference between ECC and LCC in terms of PFSR6, PFS and OS. The results in patients with non-L-sarcomas do not justify further investigation of this combination. Clinical trial information: NCT03590210 .
Patient perspectives on CLL treatment side effects: A sub-analysis of the VOICE survey.
Authors: Constantine Si Lun Tam, Javier Pinilla-Ibarz, Volkan Karakus, Miguel Pavlovsky, Martin Šimkovič, Stephan Stilgenbauer, Ana Cristina Fenili, Miguel Augusto Miroli, Carolina Garcia Castillo, Kathryn Huntley, Catherine Moura, Fernando Piotrowski, Mervat Mattar
Journal: Journal of Clinical Oncology (2023)

7534 Background: Treatment for chronic lymphocytic leukemia (CLL), including chemoimmunotherapy and targeted drugs, is associated with various adverse events. We surveyed patients with CLL about their knowledge and attitudes regarding treatments and “side effects” (SEs), a more widely understood term for adverse events. Methods: Clinicians and patient advocacy group representatives developed and distributed a survey from March through December 2022 in 12 countries to patients with CLL who underwent ≥1 line of treatment. The anonymous survey was available via an electronic platform, digital questionnaires (.pdf), or paper forms. This sub-analysis includes items regarding SEs during treatment intervals, although the SEs queried were not comprehensive. Results: Treatment SEs had a moderate or high impact on 27%–43% of patients in every domain queried (Table). Most patients (300/370; 81%) discussed SEs with their physicians “always” or “sometimes”, but (117/277) were seeking more information about the benefits and SEs associated with their treatment, primarily via the internet. When asked how they would respond to common SEs, most patients would consult their physician first . Notably, &gt;10% of them would continue treatment normally if they experienced arrhythmias or cardiac problems, and 21% would continue if they developed hypertension (Table). A similar proportion (11%) would continue treatment if they had an infection, while 23% of them would consider stopping treatment without medical advice if they developed skin cancer. Conclusions: These results show the impacts of SEs from CLL treatment affect substantial numbers of patients in multiple life areas. The responses suggest that despite patient-physician communication about SEs, there is a need to help patients find reliable information about their treatments online as well. Finally, patients’ willingness to stop or continue treatment in the event of various SEs, including cardiovascular or oncologic events, indicates a critical knowledge gap regarding the risk associated with these events. The real-world data presented herein highlights areas in which improved patient education initiatives could directly improve patient outcomes. [Table: see text]
The impact of demographic factors on patients with intraosseous well-differentiated osteosarcoma.
Authors: Madison Cook, Xinxin Wu, Darby Keirns, Peter T. Silberstein, Beau Hsia
Journal: Journal of Clinical Oncology (2023)

e23502 Background: Well-differentiated intraosseous osteosarcoma (WDIO) is a rare cancer that primarily affects the medullary cavity of the femur and tibia. While WDIO accounts for only 2% of osteosarcomas, 10% of patients do not survive past 5 years. Due to its rare nature, there is difficulty diagnosing WDIO, and as such, patients present in later stages of the disease with more secondary complications. There is no standard of treatment for WDIO. The socioeconomic factors of WDIO have yet to be addressed in literature using data from the NCDB. The purpose of this study is to analyze the demographic and socioeconomic factors of patients diagnosed with WDIO, using the National Cancer Database (NCDB) to better understand its epidemiology. Methods: The National Cancer Database (NCDB) was used to create a retrospective cohort analysis of histologically-confirmed WDIO patients (N = 30) from 2004 – 2020. Regression analysis was performed to interpret incidence trends and descriptive statistics on specific demographic factors (sex, race, age, insurance status, income, type of treatment, facility type, and Charleson-Deyco score) on patients with WDIO. Results: There were a total of 30 patients in the NCDB database identified with a diagnosis of WDIO. From 2004 – 2020, there has been an increasing incidence rate (R2 = 0.3). The mean age of WDIO diagnosis is 37.9 (SD = 18.6 range = 8 – 80 years). The long bones of the upper and lower limbs accounted for 63.4% of the primary sites of the cancer. More women (63.3%) than men were diagnosed. The majority (83.3%) of the patients had Charlson-Deyo comorbidity scores of 0. The upper income quartile contained the highest percentage of patients (42.3%) compared to each of the other lower quartiles. There were more privately insured patients (63.3%) than patients on Medicaid/Medicare. Over half of the patients (51.9%) came from metropolitan areas with a population greater than 1 million. More than half of the patients were treated at research/academic facilities (51.3%). The main form of treatment in patients with WDIO was radical excision with limb salvage (60%). Local and partial resection occurred in 30% of the cases. Conclusions: This study addresses a significant gap in knowledge on the diagnosis of WDIO and its relation to socio-demographic factors. The majority of the patients present with WDIO in the long bones of the upper and lower body, which is concurrent with previous reports of WDIO. From our analysis, patients with WDIO tend to be in the upper income quartile, live in densely-populated urban areas, and receive radical excision surgery in academic programs. This preliminary research on the impacts of demographic and socioeconomic factors on WDIO could bring more awareness to its diagnosis. Further research on the impacts of these demographics on treatment options and overall prognosis would significantly enhance our knowledge regarding the social inequality surrounding WDIO.
waveLINE-006: A phase 2 study of the safety and efficacy of zilovertamab vedotin as monotherapy or in combination in patients (pts) with aggressive and indolent B-cell malignancies.
Authors: Pier Luigi Zinzani, Jiri Mayer, Ohad Benjamini, Alejandro Berkovits, Ingrid Glimelius, Don A. Stevens, Arvind Chaudhry, Ahmet Muzaffer Demir, Ramón Garcia Sanz, Won Seog Kim, Fei Li, Janusz Halka, Ana Marin-Niebla, Muhit Ozcan, Ewa Paszkiewicz-Kozik, Armando Santoro, Yixin Ren, Uzor Ogbu, Patricia Marinello, Wojciech Jurczak
Journal: Journal of Clinical Oncology (2023)

TPS7595 Background: ROR1 is a transmembrane protein expressed in hematologic malignancies. Zilovertamab vedotin (ZV) is an antibody-drug conjugate comprising a humanized IgG1 monoclonal anti-ROR1, a proteolytically cleavable linker, and the antimicrotubule agent monomethyl auristatin E. Nemtabrutinib is a reversible inhibitor of Brutons tyrosine kinase (BTK). The combination of ZV and a BTKi has the potential for improved responses in B-cell malignancies. The waveLINE-006 study (NCT05458297) is designed to investigate safety and efficacy of ZV as monotherapy or in combination with nemtabrutinib in pts with B-cell malignancies. Methods: Eligible pts are ≥18 years old with biopsy-proven and/or histologically confirmed mantle cell lymphoma (MCL), Richters transformation (RT), chronic lymphocytic leukemia (CLL), or follicular lymphoma (FL), relapsed or refractory (R/R) disease, ECOG performance status of 0 to 2, and adequate organ function (table). Approximately 275 pts will be enrolled in 6 cohorts (A-F; see table). In cohorts A and B, patients will receive ZV 2.5 mg/kg IV Q3W. In cohort C, 30 patients will be enrolled in a safety run-in phase of ZV in combination with nemtabrutinib, then an additional 15 patients will receive the RP2D of the combination. Patients in cohort D (schedule optimization) will be randomized 1:1 to receive ZV 2.5 mg/kg IV Q3W (arm 1) or ZV 2.0 mg/kg IV Q2/3W (arm 2). Patients in cohorts E and F (efficacy expansion) will receive the dose and schedule of ZV determined during schedule optimization. Each recipient of ZV or nemtabrutinib will receive the assigned intervention until disease progression, unacceptable toxicity, or other discontinuation criteria are met. Tumor scans will be performed at baseline, then Q12W up to week 108, then Q24W thereafter. Adverse events (AEs) will be monitored and will be graded per NCI CTCAE version 5. The primary end points are the safety and tolerability of ZV alone (cohort D) and in combination with nemtabrutinib (cohort C), and the objective response rate of ZV alone (cohorts A, B, D, E, and F) and in combination with nemtabrutinib (cohort C). The secondary end points are the duration of response of ZV alone (cohorts A, B, D, E, and F) and in combination with nemtabrutinib (cohort C) and the safety and tolerability of ZV alone (cohorts A, B, E, and F). Clinical trial information: NCT05458297 . [Table: see text]
Association of medical debt and cancer mortality in the US.
Authors: Xin Hu, Zhiyuan Zheng, Kewei Sylvia Shi, Robin Yabroff, Xuesong Han
Journal: Journal of Clinical Oncology (2023)

6505 Background: Medical debt is associated with non-medical and medical financial hardship, such as food and housing insecurity, as well as delaying or forgoing recommended health care. This study examines county level associations between medical debt and cancer mortality in the US. Methods: We conducted a county level ecological study, using 2018 medical debt data from the Urban Institute linked with 2015-2019 mortality data from the National Centers for Health Statistics. All US counties with non-missing information on medical debt and other covariates were included. Primary outcomes were age-adjusted mortality rates per 100,000 person-years for all malignant cancers and by cancer type. Multivariable linear mixed models were used to estimate the association of percent of population with medical debt with cancer mortality, adjusting for county level sociodemographic characteristics. Additional analyses examined the association between median amount of medical debt per person and cancer mortality for the subset of counties with these data. Models were weighted by county level population size, with standard errors clustered at the state level. Results: Among 2,943 counties, an average of 19.8% of the population had medical debt, ranging from 0% to 53.6% across counties. Higher percentages of the population with medical debt were observed in non-metro areas, counties with higher percentages of non-Hispanic Black people, adults without high school education, living below poverty level, uninsured, or unemployed. One percentage point increase in the population with medical debt was associated with a 1.12 (95% CI=1.02-1.22) increase in age-adjusted mortality rate (per 100,000 person-years) for all malignant cancers, a 0.47 (95% CI=0.43-0.52) increase for lung cancer, a 0.09 (95% CI=0.07-0.11) increase for colorectal cancer, and a 0.06 (95% CI=0.04-0.07) increase for female breast cancer. Among 1,949 counties with the amount of medical debt available, each $100 increase in median medical debt was associated with a 0.86 (95% CI=0.52-1.21) increase in age-adjusted mortality rate for all malignant cancers. Associations between increases in median medical debt and increased mortality rates were statistically significant for major cancer types. Conclusions: Medical debt is associated with significantly higher cancer mortality at the county level. Policies increasing access to affordable health care may improve cancer outcomes. [Table: see text]
Estimating burden of cardiovascular disease among survivors of breast, colorectal, lung, and prostate cancer in the detroit research on cancer survivors (ROCS) cohort.
Authors: Vidhya Nair, Michael S. Simon, Ana Barac, Sreejata Raychaudhuri, Kerryn Reding, Richard Cheng, Julie Ruterbusch, Alexi Vasbinder, Jennifer Lynn Beebe-Dimmer
Journal: Journal of Clinical Oncology (2023)

12082 Background: With new advances in cancer treatment, cancer-specific mortality has decreased by 31% over the past 3 decades. The growing number of cancer survivors has led to increased risk of other chronic conditions including cardiovascular disease (CVD), which has become an important competing cause of mortality. This study evaluates the incidence of CVD, including heart failure (HF), myocardial infarction (MI), coronary artery disease (CAD), atrial fibrillation (AF) and stroke after cancer in the Detroit ROCS cohort. Methods: ROCS is an African American cancer survivorship cohort that enrolled participants residing in the tri-county Detroit Metropolitan area. This study included survivors of breast, colorectal, lung, and prostate cancer who provided socio-demographic and clinic information on self-administered questionnaires. We calculated incidence as percentages and rates per 1,000 person-years of HF, MI, CAD, AF, and stroke after cancer. Multivariate logistic regression analysis was used to evaluate the relationship between socio-demographic and clinical predictors of CVD by using factors with p-value &lt; 0.1. Results: After excluding patients with pre-existing CVD or lack of data on comorbidities, the study cohort consisted of 2,865 participants. The mean (SD) age at cancer diagnosis was 60.3 (9.4) years with median follow up of 3.0 (1.0-9.3) years. The incidence rate for any CVD was 23.3 per 1,000 person-years. In the study sample, stroke was the leading CVD, followed by HF, AF, CAD and MI. Lung cancer survivors had the highest incidence of CVD followed by prostate, breast, and colorectal cancer. Age at cancer diagnosis, household income, insurance, aspirin, smoking, body mass index, hypertension, diabetes, and high cholesterol were included in the final model. In the multivariate analysis, decreased household income [OR 1.26 (95% CI 1.05-1.52)], prior aspirin use [OR 1.83 (95% CI 1.34-2.49)], and history of hypertension [OR 1.71 (95% CI 1.20-2.44)] were associated with higher odds of CVD. Conclusions: CVD is a relatively common outcome within years after cancer diagnosis in an African American survivorship cohort. Intervention should focus on the possible impact of socioeconomic variables and control of hypertension in reducing the risk of CVD after cancer. [Table: see text]